Why Molly May Be More Dangerous and Deadly If You're a Woman

Popping molly is more complicated than you think—especially when you're a girl.

Hours after taking ecstasy, a teenage girl lies unconscious in a hospital bed in Essex, England. Her mouth gapes open and a tangle of life support tubes snake around her neck. "There's a drug dealer out there selling poison," a policeman tells the press. "We suggest someone stops him before someone else ends up in hospital or dead."

In November, it will be 20 years since the death of English teenager Leah Betts. After dropping a pill at her 18th birthday party, she collapsed and started convulsing. She spent five days in a coma before her life support machine was turned off. Since then, this image of her—with tangled tubes and gaping mouth—has become ingrained in the minds of most British people. In the months after her death, she became a literal poster child for anti-drugs education. Her picture appeared in newspapers, school classrooms, and on billboards captioned: "Sorted—just one ecstasy tablet took Leah Betts." It's still one of the most high-profile female ecstasy deaths of all time.

While in the 90s the public were shocked to discover that a pretty, suburban girl had died after taking ecstasy, now it's rare to find a pop starlet who hasn't sung about popping molly. This year alone, there's been a string of female ecstasy-related deaths: A 19-year-old died while celebrating her birthday at Ecostage festival in Washington, an 18-year-old from Colorado Springs was killed after taking molly cut with opiates, and a Scottish teenager died while partying in Ibiza. The 2015 Global Drugs Survey found that women were nearly two times more likely than men to get admitted to hospital after taking MDMA last year. The online survey was filled out by 23,000 ecstasy users from 25 different countries, and showed that 1.3 per cent of women sought medical treatment after taking the drug versus 0.7 per cent of men. Women also reported more mood problems, paranoia, and hallucinations.

Despite these potentially increased dangers for women, there's been very little research into the impact of gender on ecstasy. In fact, twenty years after Betts' death, we're only just starting to learn how ecstasy affects women. Gender-focussed studies are small in sample size and, while not all scientists report differences in the way that men and women react to the drug, there is strong enough evidence to suggest that there might be a chemical difference in the way men and women react to it.

Ecstasy—also known as MDMA in its powdered form—alters your mood by stimulating the release of three feel-good neurotransmitters: Serotonin, dopamine and norepinephrine. Your body usually rewards you with a dopamine hit to reinforce positive behaviours like exercise and eating. Meanwhile, serotonin is responsible for maintaining mood balance. The drug makes you feel good because your brain is hit with a rush of these neurotransmitters all at once. Eventually stocks deplete, and that's when you find yourself crying on a comedown to Kelly Clarkson's back catalogue a day later.

A study from 2013 conducted on men and women who had used ecstasy at least 25 times showed that the drop in serotonin levels affected the women's mood more than men's. Researchers reported: "Women polydrug [who use two or more drugs at the same time]ecstasy users appear to be more susceptible than men to the effects of lowered serotonin levels.If use of ecstasy alone or in conjunction with other drugs causes progressive damage of serotonin neurons, women polydrug ecstasy users may become susceptible to clinical depression."

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These results are echoed by other studies where scientists ask drug users to explain their experiences. In 2012, an Australian group of scientists placed fliers in Sydney and Melbourne, put out an advert in Beat magazine, and advertised on websites looking to speak to regular ecstasy users. Of the 268 people they spoke to, they found that in general women reported worse sleep quality and lower scores on the mental health scale than men after taking ecstasy. In 2002, scientist Suzanne Verheyden found that women experience higher levels of depression mid-week after taking MDMA and in 2000, Matthias Leichti revealed that women are more likely to experience anxiety and hallucinate while on the drug.

"Women appear to experience the psychoactive effects of MDMA more strongly than men, and they have more negative effects such as feeling anxious, depressed, dizzy, or sedated while under the influence," said Gillinder Bedi, an assistant professor of clinical psychology at Columbia University. "They also appear to have greater increases in heart rate and temperature after MDMA than men. On the other hand, blood pressure increases after MDMA may be higher in men than in women."

In 2013, another group of scientists gave 32 volunteers a dose of MDMA (relative to their body weight) and found that it had different effects on women and men as the drug took effect. During empathy tests, only the women found it harder to recognize sad faces after taking the drug, and female subjects also struggled to recognize fearful faces. Men experienced a much greater increase in empathic concern than women, but their increased empathy only brought them up to the same level exhibited by women who were given placebos and weren't high. Go figure.

What could be causing these differences? There are a whole load of variables which change how you react to drugs. Factors like your body weight, whether you're taking more than one kind of drug, whether you're drinking, and whether you're in a hot environment all play a part. Scientists also hypothesize that women might just be better than men at recognising emotional and physical changes in themselves. But signs indicate that the fluctuating hormones of the female reproductive system could also be added to this list. Your period may affect your high, your comedown, and your likelihood of being hospitalized after taking MDMA.

The changing levels of oestrogen and progesterone that women experience during their menstrual cycle can affect neurotransmitter systems, like the serotonin system. This year, scientists published the results of a study where they gave MDMA to male rats, female rats, and male and female rats which had their testicles and ovaries removed. They found the drug had the strongest effect on female rats with an intact reproductive system, concluding that "the increased sensitivity of the females can be explained by an increased reactivity of the serotonin system due to the effect of ovarian hormones." Research has also shown that the effects of other stimulants, like cocaine, vary in women because of changes in the levels of female hormones during the menstrual cycle. For example, you're potentially more sensitive to amphetamines just before ovulation. This suggests that not only do women react differently to some drugs than men, they might also react differently depending on whether they're on their period or not.

Your period may affect your high, your comedown, and your likelihood of being hospitalized after taking MDMA.

Unfortunately, research around this is very limited. While this is partially because of tight regulations surrounding human drug studies, it's also down to the exact reason why women might react differently to MDMA in the first place: Periods. According to David Erritzøe, a medical doctor and post-doctoral researcher from Imperial College London, women are often skipped out of molecular imaging drugs studies—the only way to access neurotransmitter systems in the living human brain—for two grounds.

Firstly, even though women can be screened for pregnancy, they're left out just in case they are pregnant, as the studies involve radioactivity and pose a 'low risk' to their unborn child. Secondly, there's the possibility our changing hormone levels could skew results."Studies cost a fortune so you try to reduce subjects to the minimum. But, if you want to look at women, you need to include extra people so you can figure out what is caused by where they are in their menstrual cycle," he said. "It means often studies just look at men. I recently looked at all the imaging data about drugs, alcohol, and the dopamine system and there were 10 times more males than females in the studies."

His opinion is supported by a paper written by neuroscientist Kelly Allott in 2006. Allott's paper was basically a 'Best Of' round-up of the 38 gender-related ecstasy studies that had been published up until that point. In it, she explains the key issue with the lack of female-based research. "Findings from predominantly male samples are often generalized to females. This is problematic given there are pharmacokinetic [the way a drug moves through the body] and pharmacodynamic [the effect of drugs on the body] differences between males and females."

Women are skipped out of studies because our hormone levels skew results. But because we're skipped out of studies, it's hard to know for sure exactly if or how our hormone levels really do skew results. This means that if there truly are gender differences in the way we react to drugs, the advice that we are currently given about taking substances is based on data that doesn't necessarily fully apply to women.

This is especially important when you look back at the case of Leah Betts. She was killed by hyponatremia, a condition that affects MDMA users because the drug both makes you feel excessively thirsty and stimulates the secretion of the antidiuretic hormone AVP (or ADH), which stops you urinating.

Little was known about the risks of MDMA-induced hyponatremia in the 90s, so ecstasy users were encouraged to stay very hydrated. On the night she died, Betts had drunk more than three litres of water. Her blood sodium levels had become dangerously diluted and her cells had flooded with water. Within hours, her brain had swelled and fatally squeezed against her skull. Professor John Henry, an expert in toxicology, gave evidence at the inquest into Leah's death. Looking back on the incident in 2005, he told the BBC: "The original advice—'If you take E, take water'—that was fatal advice."

In fact, by ignoring women in drugs studies, researchers make the dangers of MDMA an issue of sexism as well as science.

Turns out hyponatremia is more common in female ecstasy users than male. In fact, almost 90 per cent of cases of ecstasy-induced hyponatraemia reported to the California Poison Control System over a five-year span involved women. A 2011 study also showed that MDMA might significantly increase levels of AVP hormones in women, but not in men. Plus, when scientists tested the the blood concentration of ravers at Awakenings Festival in the Netherlands they found that 27.3 per cent of the women they tested had blood so diluted that they had mild hyponatremia, compared to just three percent of the men. They write that this might be because AVP is regulated by oestrogen: "Differences in MDMA metabolism or in the pituitary sensitivity to the [AVP] secreting effect of MDMA or its metabolites, perhaps related to the phase of the menstrual cycle, could explain [women's] individual tendency to develop hyponatraemia after doses of MDMA not considered to be excessive."

If there is potentially more of a risk for women to become physically or mentally ill after taking MDMA, and if that risk is potentially related to our stage of the menstrual cycle—it's something that needs to be looked into. In fact, by ignoring women in drugs studies, researchers make the dangers of MDMA an issue of sexism as well as science.

Until then, you might want to consider whether your period will make your comedown a whole lot worse the next time you drop molly.